Atypical Chronic Myeloid Leukemia: New Developments from Molecular Diagnosis to Treatment
Abstract
:1. Introduction
2. Clinical Presentation and Prognostic Factors
3. Diagnosis and Classification
4. New Molecular Insight
5. Differential Diagnosis
6. Treatment
6.1. Allogenic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
6.2. Cytoreductive Drugs and Erythropoiesis Stimulation
6.3. New Target Therapies
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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aCML | CNL | CMML | MDS/MPN-RS-T | MDS/MPN-U |
---|---|---|---|---|
PB leukocytosis (WBC ≥ 13 × 10 × 9/L), (neutrophilia and increased myeloid precursors) | PB leukocytosis (WBC ≥ 25 × 10 × 9/L) | Persistent PB monocytosis ≥1 × 109/L | Persistent Thrombocytosis (plts ≥ 450 × 109/L) | Mixed MDS and MPN features at onset, not meeting diagnostic criteria for any other MDS/MPN, MDS, or MPN neoplasm |
Myeloid precursors ≥ 10% of WBC | Myeloid precursors < 10%; segmented and banded neutrophil ≥ 80% of WBC | Plts ≥ 450 × 109/L | Plts ≥ 450 × 109/L with BM megakaryocytic proliferation and/or WBC ≥ 13 × 10 × 9/L | |
No or minimal absolute monocytosis; monocytes < 10% of WBC | Monocyte count < 1 × 109/L | Monocytes ≥ 1 × 109/L and ≥10% of the WBC | ||
<20% blasts in PB and BM | Blasts rarely in PB and <5% blasts in BM | <20% blasts in PB and BM | <1% blasts in PB and <5% blasts in BM | <20% blasts in PB and BM |
No or minimal absolute basophilia; basophils < 2% of WBC | ||||
Dysgranulopoiesis, which may include abnormal chromatin clumping | No dysgranulopoiesis | |||
Hypercellular BM with granulocytic proliferation and granulocytic dysplasia, with or without dysplasia in the erythroid and megakaryocytic lineages | Hypercellular BM with increased % of neutrophil, but neutrophil maturation appears normal | Dysplasia in 1 or more myeloid lineages * | Erythroid-lineage dysplasia, with or without multilineage dysplasia, ≥15% ring sideroblasts | Clinical and morphological features of one of MDS |
No BCR-ABL1 fusion. No evidence of PDGFRA, PDGFRB, or FGFR1 rearrangement, or PCM1-JAK2 fusion | ||||
Not meeting WHO criteria for BCR-ABL1+ CML, PMF, PV or ET | ||||
Presence of CSF3R T618I or other activating CSF3R mutation ** | Presence of SF3B1 mutation *** No t(3,3)(q21.3; q26.2), inv(3)(q21.3; q26.2), or del(5q) | No history of recent cytotoxic or growth factor therapy that could explain the MDS/MPN features |
ClinicalTrials.gov Identifier | Title | Phase | Drugs Investigated | Mechanism of Action | Setting |
---|---|---|---|---|---|
NCT03862157 | A Phase I/II Study of Azacitidine, Venetoclax and Pevonedistat in Adults With Newly Diagnosed Secondary or Therapy-Related AML | I/II | Azacitidine Venetoclax Pevonedistat | HMA BCL2 inhibition NEDD8-activating enzyme (NAE) inhibition | Untreated AML, aCML, MDS, and MDS/MPN overlap syndromes |
NCT03878524 | Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: PRIME | Ib | Different combinations of novel drugs | Relapsed refractory hematological malignancies and solid cancers | |
NCT04637009 | A Phase 1 Study of Safety, Pharmacokinetics and Preliminary Activity of TAS1553 in Subjects With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML), and Other Myeloid Neoplasms | I/II | TAS1553 | Ribonucleotide reductase (RNR) inhibition | Untreated AML, secondary AML, accelerated phase MPN, chronic/accelerated phase MPN-unclassifiable and MDS-MPN, and aCML |
NCT01787487 | Evaluation of Ruxolitinib and Azacytidine Combination as a Therapy for Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm | II | Azacitidine Ruxolitinib | HMA Jak2 inhibition | myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm |
NCT02158858 | A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis) | I/II | CPI-0610 | BET protein inhibition | previously treated Acute Leukemia, Myelodysplastic Syndrome, and Myelodysplastic/Myeloproliferative Neoplasms and Myelofibrosis |
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Castellino, A.; Santambrogio, E.; Rapezzi, D.; Massaia, M. Atypical Chronic Myeloid Leukemia: New Developments from Molecular Diagnosis to Treatment. Medicina 2021, 57, 1104. https://doi.org/10.3390/medicina57101104
Castellino A, Santambrogio E, Rapezzi D, Massaia M. Atypical Chronic Myeloid Leukemia: New Developments from Molecular Diagnosis to Treatment. Medicina. 2021; 57(10):1104. https://doi.org/10.3390/medicina57101104
Chicago/Turabian StyleCastellino, Alessia, Elisa Santambrogio, Davide Rapezzi, and Massimo Massaia. 2021. "Atypical Chronic Myeloid Leukemia: New Developments from Molecular Diagnosis to Treatment" Medicina 57, no. 10: 1104. https://doi.org/10.3390/medicina57101104